1. Field of the Invention
The present invention relates to a novel sulfonamide derivative. More particularly, it relates to a novel sulfonamide derivative or a salt thereof which shows a strong inhibitory activity against cysteine protease such as calpain, cathepsin B, cathepsin H, cathepsin L, and papain.
2. Description of the Related Art
As the in vivo action of cysteine protease, which papain, calpain, cathepsin and the like belong to, has been elucidated, its abnormal accentuation has been found to cause various diseases. Accordingly, cysteine protease inhibitors have been used as remedies for such diseases. For example, calpain inhibitors have been reported to be effective in an animal model suffering from muscular dystrophy, cataract, myocardial infarction, stroke, while cathepsin inhibitors have been reported to be effective for metastasis of cancer, amyotrophia, osteoporosis, hypercalcemia and the like.
As cysteine protease inhibitors, peptidyl aldehyde derivatives are well known. For example, Leupeptin [Journal of Antibiotics, 22, 183 (1969)], Strepin P-1 [Agricultural and Biological Chemistry, 49, 799 (1985)], Staccopins P1, P2 [Agricultural and Biological Chemistry, 51, 861 (1987)] and the like have been isolated from a microbial culture medium. In addition, various compounds have been synthesized. For example, MDL 28170 [Biochemical and Biophysical Research Communications, 157, 1,117 (1988)] and Calpeptin [Journal of Enzyme Inhibition, 3, 195 (1990)] are well known. Under the present conditions, most of the N-termini of these peptidyl aldehyde derivatives are free amino acid or amide derivative thereof or carbamate thereof, and few have been reported about N-terminal in the form of sulfonamide [Japanese Patent Application Laid-open No. 268145-1990; Journal of Antibiotics, 41, 220 (1988); Journal of Biochemistry, 98, 975 (1985); Developmental Biology, 105, 246 (1984); Journal of Pharmacobio-Dynamics, 6, 643 (1983); Japanese Patent Application Laid-open No. 054157-1982; Proceedings of National Academy of Science of the U.S.A., 76, 1,131 (1979); Japanese Patent Application Laid-open No. 137951-1975]. Compounds having stronger cysteine protease inhibitory activity have been sought.